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Table 2 The Dynamic Changes Occurring in the Immune Microenvironment after EGFR Inhibition in an EGFR-Mutant Transgenic Mouse Model

From: Role of the dynamic tumor microenvironment in controversies regarding immune checkpoint inhibitors for the treatment of non-small cell lung cancer (NSCLC) with EGFR mutations

Effect of EGFR-TKIs on tumor immune Microenvironment Early Treatment Later Treatment Throughout Treatment
Antitumor Activity Tumor burden↓ Tumor burden↓ Tumor burden↓
Tumor size↓ Tumor size↓ Tumor size↓
Expression of Immune Checkpoint Molecules PD-L1↓a PD-L1↓a PD-L1↓a
PD-1↓b PD-1↓b PD-1↓b
CTLA-4↓b CTLA-4↓ b CTLA-4↓b
TIM-3↓b TIM-3↓b TIM-3↓b
Lymphocyte Infiltration CD3+ lymphocytes ↑ CD3+ lymphocytes +/−  
CD8+ T cells↑ CD8+ T cells  
Foxp3+ Tregs↓ Foxp3+ Tregs  
Macrophage Infiltration CD11b + Myeloid Cells↑ CD11b + Myeloid Cells↑ CD11b + Myeloid Cells↑
PMN-MDSCs +/− PMN-MDSCs +/− PMN-MDSCs +/−
M-MDSCs↑ M-MDSCs↑ M-MDSCs↑
DCs↑ DCs+/−  
M1-TAM↑ M1-TAM↓  
M2-TAM↓ M2-TAM↓ M2-TAM↓
Cytokine Secretion IL-10 +/− IL-10↑  
CCL-2 +/− CCL-2↑  
  1. PD-L1 Programmed death-ligand 1, PD-1 Programmed cell death protein 1, CTLA-4 The cytotoxic T-lymphocyte–associated antigen 4, TIM-3 T-cell immunoglobulin and mucin-domain containing-3, PMN-MDSCs Polymorphonuclear MDSCs, M-MDSCs Mononuclear MDSCs, IL-10 Interleukin 10, CCL-2 The chemokine (C- C motif) ligand 2
  2. a: PD-L1 expression after EGFR-TKI monotherapy in both CD45+ immune cells and CD4 − tumor cells;
  3. b: PD-1, CTLA-4, and TIM-3 expression on CD3+ lymphocytes;
  4. +/−: Remained unchanged
  5. ↑: increased
  6. ↓: decreased